The major thrust of our research program during the past few years has been to understand the early events of the intrinsic and extrinsic pathways of blood coagulation. Accordingly, considerable effort has been made to isolate and characterize bovine factor XII and factor XI, in addition to prekallikrein and high molecular weight kininogen. These proteins are involved in the contact phase of the intrinsic pathway of blood coagulation, and their interaction eventually leads to the conversion of factor IX to factor IXa. Results from a number of laboratories, including our own, have also implicated the contact phase of coagulation in the initiation of the extrinsic pathway. In these studies, it has been shown that factor XIIa will activate factor VII. Accordingly, our work during the next year will focus on a study of those events that lead to the triggering of both the intrinsic and extrinsic pathways of coagulation in an attempt to understand on a molecular basis the mechanisms by which these reactions occur. Initially, these investigations will focus on the bovine system where large amounts of starting material are available. Eventually, however, it is planned that similar studies on the contact system will be carried out on the human system. BIBLIOGRAPHIC REFERENCES: Di Scipio, R.G., Hermodson, M.A., Yates, S.G., and Davie, E.W., A Comparison of Human Prothrombin, Factor IX (Christmas Factor), Factor X (Stuart Factor), and Protein S, Biochemistry 16, 698 (1977). Fujikawa, K., Walsh, K.A., and Davie, E.W., Isolation and Characterization of Bovine Factor XII (Hageman Factor), Biochemistry 16, 2270 (1977).